| 1. |
- Amini, Hashem, et al.
(författare)
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Comparison of ultrasound and autopsy findings in pregnancies terminated due to fetal anomalies
- 2006
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 85:10, s. 1208-1216
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To compare antenatal diagnoses with autopsy findings in pregnancies terminated after ultrasound detection of fetal anomalies. A second aim was to study the quality of antenatal fetal diagnosis over time. Design. Retrospective, multicenter study over two consecutive six-year periods in Uppsala and Stockholm. Setting. Cases were identified through fetal autopsy reports. Subjects. Three hundred and twenty-eight fetuses from pregnancies terminated between 1992 and 2003 because of ultrasonographically diagnosed anomalies. Main outcome measures. The findings at the last ultrasound examination were compared with the autopsy reports. Results. In 299 cases (91.2%) ultrasound findings either exactly matched or were essentially similar to the autopsy findings. In 23 cases (7%) ultrasound findings were not confirmed at autopsy, but the postnatal findings were at least as severe as the antenatal ones. In six cases (1.8%) termination was performed for an anomaly which proved to be less severe than was predicted by ultrasound. The number of such cases was the same in both six-year periods, while the total number of cases increased from 113 in the first to 215 in the second period. Fetal examination provided further diagnostic information in 47% of the cases. In 10% a syndrome was disclosed. Conclusion. Termination of pregnancy was not always based on a correct antenatal diagnosis. All fetuses but one from terminated pregnancies had evident anomalies. In six cases (1.8%) the decision to terminate was based on suboptimal prognostic and diagnostic information. Fetal autopsy by an experienced perinatal pathologist is essential to provide a definitive diagnosis.
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| 2. |
- Baer, Katharina, 1984-, et al.
(författare)
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Aspects of Parameter Sensitivity for Series Hydraulic Hybrid Light-Weight Duty Vehicle Design
- 2016
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Ingår i: Proceedings of the 9th FPNI Ph.D. Symposium on Fluid Power (FPNI2016). - : American Society of Mechanical Engineers. - 9780791850473
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Konferensbidrag (refereegranskat)abstract
- Hybridization of a vehicle’s drivetrain can in principle help to improve its energy efficiency by allowing for recuperation of kinetic energy and modulating the engine’s load. How well this can be realized depends on appropriate sizing and control of the additional components. The system is typically designed sequentially, with the hardware setup preceding the development and tuning of advanced controller architectures. Taking an alternative approach, component sizing and controller tuning can be addressed simultaneously through simulation-based optimization.The results of such optimizations, especially with standard algorithms with continuous design variable ranges, can however be difficult to realize, considering for example limitations in available components. Furthermore, drive-cycle based optimizations are prone to cycle-beating. This paper examines the results of such simulation-based optimization for a series hydraulic hybrid vehicle in terms of sensitivity to variations in design parameters, system parameters and drive cycle variations. Additional relevant aspects concerning the definition of the optimization problem are pointed out.
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| 3. |
- Baer, Katharina, et al.
(författare)
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Component Sizing Study for a Light-Duty Series Hydraulic Hybrid Vehicle in Urban Drive Cycles
- 2013
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Konferensbidrag (refereegranskat)abstract
- With the focus on energy efficiency for many different kinds of vehicle applications,hybridization is considered a possible solution to reduce fuel consumption. While hybrid electric concepts are already available for passenger vehicles, and also considered for heavier applications, hybrid hydraulic alternatives have been mainly limited to the latter, which benefit most from the higher power density available. To study the different hybrid architectures and applications, a modeling framework for the system design is developed using the simulation tool Hopsan from Linköping University. Previously, the model of a series hydraulic hybrid vehicle was introduced, a light-duty vehicle simulated over two standard urban drive cycles, and its potential for further work established. In this paper, the model is extended by including a simple combustion engine power management to provide for more realistic propulsion of the hydraulic drivetrain, showing the potential to operate a series hydraulic hybrid vehicle’s engine in more efficient regions. Additionally, the design is studied concerning the effects of a variation of key component sizes on the accuracy and energy efficiency objectives. Instead of subjecting the system to (multi- objective) optimization, at this stage the individual component’s influence is studied, and the objectives are dealt with separately from each other to eliminate the need for compromise between them, both to gain a better understanding of the interdependencies.
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| 4. |
- Baer, Katharina, et al.
(författare)
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Design Study and Parameter Optimization for a Light-Weight Series Hydraulic Hybrid Vehicle
- 2015
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Konferensbidrag (refereegranskat)abstract
- Hydraulic hybrid drives are one potential way of improving the fuel efficiency of vehicles, including the possi-bility of recuperating braking energy in a hydraulic accumulator. The high power density of fluid power is mainly advantageous for heavy vehicles, or duty cycles characterized with frequent braking and acceleration. For smaller vehicles, hydraulic hybrid drives are thus most interesting under urban and suburban driving conditions. Amongst the existing architectures, the series hydraulic hybrid offers the advantage of operating the internal combustion engine independently of the vehicle speed, at the cost of a less efficient transmission path than a purely mechanical one. Previously, a series hydraulics hybrid light-duty vehicle was modelled in the transmission-line modelling (TLM)-based simulation software Hopsan from the division of Fluid and Mechatronic Systems (Flumes) at Linköping University. This paper studies through simulation-based optimi-zation how the fuel-optimal vehicle design is affected by various mixes of urban and suburban driving requirements. Both the system’s hardware and the parameters of a basic control strategy are considered. The results show quite similar designs for most performance requirements combinations, and can be the base for further studies addressing additional requirements, conditions and objectives.
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| 5. |
- Baer, Katharina, 1984-, et al.
(författare)
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Framework for simulation-based simultaneous system optimization for a series hydraulic hybrid vehicle
- 2019
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Ingår i: International Journal of Fluid Power. - : Taylor & Francis. - 1439-9776 .- 2332-1180. ; 20:1, s. 27-51
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Tidskriftsartikel (refereegranskat)abstract
- Hybridisation of hydraulic drivetrains offers the potential of efficiency improvement for on – and off-road applications. To realise the advantages, a carefully designed system and corresponding control strategy are required, which are commonly obtained through a sequential design process. Addressing component selection and control parameterisation simultaneously through simulation-based optimisation allows for exploration of a large design space as well as design relations and trade-offs, and their evaluation in dynamic conditions which exist in real driving scenarios. In this paper, the optimisation framework for a hydraulic hybrid vehicle is introduced, including the simulation model for a series hybrid architecture and component scaling considerations impacting the system’s performance. A number of optimisation experiments for an on-road light-duty vehicle, focused on standard-drive-cycle-performance, illustrate the impact of the problem formulation on the final design and thus the complexity of the design problem. The designs found demonstrate both the potential of energy storage in series hybrids, via an energy balance diagram, as well as some challenges. The framework presented here provides a base for systematic evaluation of design alternatives and problem formulation aspects.
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| 6. |
- Baer, Katharina, et al.
(författare)
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Modeling of a Series Hybrid Hydraulic Drivetrain for a Light-Duty Vehicle in Hopsan
- 2013
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Ingår i: Conference proceedings. - Linköping, Sweden : Linköping University Electronic Press. - 9789175195728 ; , s. 107-112
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Konferensbidrag (refereegranskat)abstract
- Hydraulic hybrids continue to receive attention as a possible solution in the search for improved fuel economy for different vehicle types. This paper presents a model for a series hydraulic hybrid light-duty vehicle, developed in the Hopsan simulation tool of Linköping University’s Division of Fluid and Mechatronic Systems (Flumes). Focusing on the hydraulic transmission which employs a pump control based on the hydraulic accumulator’s state-of-charge (SoC), several simplifications were made, especially concerning mechanical components. Simulation over two urban standard cycles shows promising results concerning dynamic performance and energy recuperation potential, provided sufficient component sizing to compensate for the mechanical limitations. This paper lays the foundation for both a further refined model - suitable for optimizing the full drivetrain, including component sizing and controller parameterization - and the development of comparable models for parallel and power-split hybrid architectures.
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| 7. |
- Baer, Katharina, 1984-, et al.
(författare)
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Robustness and performance evaluations for simulation-based control and component parameter optimization for a series hydraulic hybrid vehicle
- 2020
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Ingår i: Engineering optimization (Print). - : Taylor & Francis. - 0305-215X .- 1029-0273. ; 52:3, s. 446-464
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Tidskriftsartikel (refereegranskat)abstract
- Simulation-based optimization is a useful tool in the design of complex engineering products. Simulation models are used to capture numerous aspects of the design problem for the objective function. Optimization results obtained can be assessed from various perspectives. In this study, component and control optimization of a series hydraulic hybrid vehicle is used as an application, and different robustness and performance aspects are evaluated. Owing to relatively high computational loads, efficient optimization algorithms are important to provide sufficient quality of results at reasonable computational costs. To estimate problem complexity and evaluate optimization algorithm performance, the definitions for information entropy and the related performance index are extended. The insights gained from various simulation-based optimization experiments and their subsequent analysis help characterize the efficiency of the optimization problem formulation and parameterization, as well as optimization algorithm selection with respect to parallel computation capabilities for further development of the model and optimization framework.
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| 8. |
- Baer, Katharina, 1984-
(författare)
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Simulation-Based Optimization of a Series Hydraulic Hybrid Vehicle
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hybrid transmissions are characterized by their utilization of more than one form of energy storage. They have the potential to help reduce overall fuel consumption and vehicle emissions by providing the possibility of brake energy recuperation and prime mover operation management. Electric hybrids and electric vehicle drives are nowadays ubiquitous, and mechanical energy storage in flywheel has been investigated in the past. The use of fluid power technology with a combustion engine has also been investigated since the late 1970s, and is frequently revisited.Hydraulic hybridization is especially attractive for heavy vehicles with frequent braking and acceleration which benefit most from fluid power components’ high power density, typically busses, delivery or refuse vehicles, and vehicles with existing hydraulic circuits and transmissions, such as forest and construction machinery, but have been considered for smaller vehicles as well.Due to the characteristic discharge profile of hydraulic energy storage, special attention needs to be paid to control aspects in the design process to guarantee drivability of the vehicle. In this respect, simulation models can be of use in early design process stages for cheaper and faster evaluation of concepts and designs than physical experiments and prototyping, and to generate better understanding of the system studied. Engineering optimization aids in the systematic exploration of a given design space, to determine limits and potentials, evaluate trade-offs and potentially find unexpected solutions. In the optimization of a hydraulic hybrid transmission, the integration of component and controller design is of importance, and different strategies (sequential, iterative, bi-level and simultaneous approaches) are conceivable, with varying consequences for the implementation.This thesis establishes a simulation-based optimization framework for a hydraulic hybrid transmission with series architecture. Component and control parameter optimization are addressed simultaneously, using a rule-based supervisory control strategy. The forward-facing dynamic simulation model at the centre of the framework is built in Hopsan, a multi-disciplinary open-source tool developed at Linköping University. The optimization is set up and conducted for an example application of an on-road light-duty truck over standard drive cycles. Both results from these experiments as well as the framework itself are studied and evaluated. Relevant design aspects, such as explicit design relations to be considered and performance requirements for more robust design, are identified and addressed, and the optimization problem is analysed with regard to algorithm performance and problem formulation. The final result is an optimization framework that can be adjusted for further in-depth studies, for example through the inclusion of additional components or optimization objectives, and extendable for comparative analysis of different topologies, applications and problem formulations.
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| 9. |
- Baer, Katharina, et al.
(författare)
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System Parameter Study for a Light-Weight Series Hydraulic Hybrid Vehicle
- 2014
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Ingår i: PROCEEDINGS OF THE 8TH FPNI PH.D SYMPOSIUM ON FLUID POWER, 2014. - : ASME Press. - 9780791845820 ; , s. V001T03A004-
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Konferensbidrag (refereegranskat)abstract
- Amongst the hybrid vehicle propulsion solutions aiming to improve fuel efficiency, hybrid electric solutions currently receive most attention, especially on the market. However, hydraulic hybrids are an interesting alternative, especially for heavier vehicles due to higher power density which is beneficial if higher masses are moved. As a step towards a comprehensive design framework to compare several possible hydraulic hybrid architectures for a specified application and usage profile, the model of a series hydraulic hybrid vehicle was previously introduced and initially studied concerning component sizing for an exemplary light-duty vehicle in urban traffic. The vehicle is modeled in the Hopsan simulation tool. A comparably straight-forward engine management is used for the vehicle control; both pump and engine controls are based on the hydraulic accumulator’s state-of-charge. The model is developed further with respect to the accumulator component model. Based on that, the influence of several system and component parameters, such as maximum system pressure and engine characteristics, as well as controller parameters on the vehicle’s performance is analyzed. The goal is to allow for more understanding of the system’s characteristics to facilitate future optimization of the system.
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| 10. |
- Bondeson, Marie-Louise, 1960-, et al.
(författare)
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A nonsense mutation in CEP55 defines a new locus for a Meckel-like syndrome, an autosomal recessive lethal fetal ciliopathy.
- 2017
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Ingår i: Clinical Genetics. - : Wiley. - 0009-9163 .- 1399-0004. ; 92:5, s. 510-516
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in genes involved in the cilium-centrosome complex are called ciliopathies. Meckel-Gruber syndrome (MKS) is a ciliopathic lethal autosomal recessive syndrome characterized by genetically and clinically heterogeneous manifestations, including renal cystic dysplasia, occipital encephalocele and polydactyly. Several genes have previously been associated with MKS and MKS-like phenotypes, but there are still genes remaining to be discovered. We have used whole exome sequencing (WES) to uncover the genetics of a suspected autosomal recessive Meckel syndrome phenotype in a family with two affected fetuses. RNA studies and histopathological analysis was performed for further delineation. WES lead to identification of a homozygous nonsense mutation c.256C>T (p.Arg86*) in CEP55 (centrosomal protein of 55 kDa) in the affected fetus. The variant has previously been identified in carriers in low frequencies, and segregated in the family. CEP55 is an important centrosomal protein required for the mid-body formation at cytokinesis. Our results expand the list of centrosomal proteins implicated in human ciliopathies and provide evidence for an essential role of CEP55 during embryogenesis and development of disease.
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| 11. |
- Hellkvist, Anna, et al.
(författare)
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Postmortem magnetic resonance imaging vs autopsy of second trimester fetuses terminated due to anomalies
- 2019
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 98:7, s. 865-876
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Our aim was to investigate the accuracy of postmortem fetal magnetic resonance imaging (MRI) compared to fetal autopsy in second trimester pregnancies terminated due to fetal anomalies. A secondary aim was to compare the MRI evaluations of two senior radiologists.MATERIAL AND METHODS: This was a prospective study including 34 fetuses from pregnancies terminated in the second trimester due to fetal anomalies. All women accepted a postmortem MRI and an autopsy of the fetus. Two senior radiologists performed independent evaluations of the MRI images. A senior pathologist performed the fetal autopsies. The degree of concordance between the MRI evaluations and the autopsy reports was estimated as well as the consensus between the radiologists.RESULTS: Thirty-four fetuses were evaluated. Sixteen cases were associated with the central nervous system (CNS), five musculoskeletal, one cardiovascular, one urinary tract, and 11 cases had miscellaneous anomalies such as chromosomal aberrations, infections, and syndromes. In the 16 cases related to the CNS, both radiologists reported all or some, including the most clinically significant anomalies in 15 (94%; CI 70-100%) cases. In the 18 non-CNS cases, both radiologists reported all or some, including the most clinically significant anomalies in six (33%; CI 5-85%) cases. In 21 cases (62%; CI 44-78%) cases, both radiologists held opinions that were consistent with the autopsy reports. The degree of agreement between the radiologists was high, with a Cohen's Kappa of 0.87.CONCLUSIONS: Postmortem fetal MRI can replace autopsy for second trimester fetuses with CNS anomalies. For non-CNS anomalies, the concordance is lower but postmortem MRI can still be of value when autopsy is not an option.
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| 12. |
- Hoffsten, Alice, et al.
(författare)
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The value of autopsy in preterm infants at a Swedish tertiary neonatal intensive care unit 2002-2018
- 2021
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Reliable data on causes of death (COD) in preterm infants are needed to assess perinatal care and current clinical guidelines. In this retrospective observational analysis of all deceased preterm infants born <37 weeks' gestational age (n=278) at a Swedish tertiary neonatal intensive care unit, we compared preliminary COD from Medical Death Certificates with autopsy defined COD (2002-2018), and assessed changes in COD between two periods (period 1:2002-2009 vs. period 2:2011-2018; 2010 excluded due to centralized care and seasonal variation in COD). Autopsy was performed in 73% of all cases and was more than twice as high compared to national infant autopsy rates (33%). Autopsy revised or confirmed a suspected preliminary COD in 34.9% of the cases (23.6% and 11.3%, respectively). Necrotizing enterocolitis (NEC) as COD increased between Period 1 and 2 (5% vs. 26%). The autopsy rate did not change between the two study periods (75% vs. 71%). We conclude that autopsy determined the final COD in a third of cases, while the incidence of NEC as COD increased markedly during the study period. Since there is a high risk to determine COD incorrectly based on clinical findings in preterm infants, autopsy remains a valuable method to obtain reliable COD.
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| 13. |
- Johansson, Josefin, et al.
(författare)
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Loss of Nexilin function leads to a recessive lethal fetal cardiomyopathy characterized by cardiomegaly and endocardial fibroelastosis
- 2022
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Ingår i: American Journal of Medical Genetics. Part A. - : John Wiley & Sons. - 1552-4825 .- 1552-4833. ; 188:6, s. 1676-1687
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Tidskriftsartikel (refereegranskat)abstract
- The Nexilin F-Actin Binding Protein (Nexilin) encoded by NEXN is a cardiac Z-disc protein important for cardiac function and development in humans, zebrafish, and mice. Heterozygote variants in the human NEXN gene have been reported to cause dilated and hypertrophic cardiomyopathy. Homozygous variants in NEXN cause a lethal form of human fetal cardiomyopathy, only described in two patients before. In a Swedish, four-generation, non-consanguineous family comprising 42 individuals, one female had three consecutive pregnancies with intrauterine fetal deaths caused by a lethal form of dilated cardiomyopathy. Whole-exome sequencing and variant analysis revealed that the affected fetuses were homozygous for a NEXN variant (NM_144573:c.1302del;p.(Ile435Serfs*3)). Moreover, autopsy and histology staining declared that they presented with cardiomegaly and endocardial fibroelastosis. Immunohistochemistry staining for Nexilin in the affected fetuses revealed reduced antibody staining and loss of striation in the heart, supporting loss of Nexilin function. Clinical examination of seven heterozygote carriers confirmed dilated cardiomyopathy (two individuals), other cardiac findings (three individuals), or no cardiac deviations (two individuals), indicating incomplete penetrance or age-dependent expression of dilated cardiomyopathy. RNA sequencing spanning the variant in cDNA blood of heterozygote individuals revealed nonsense-mediated mRNA decay of the mutated transcripts. In the current study, we present the first natural course of the recessively inherited lethal form of human fetal cardiomyopathy caused by loss of Nexilin function. The affected family had uneventful pregnancies until week 23-24, followed by fetal death at week 24-30, characterized by cardiomegaly and endocardial fibroelastosis.
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| 14. |
- Lundgren, Markus, et al.
(författare)
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Analgesic antipyretic use among young children in the TEDDY study : No association with islet autoimmunity
- 2017
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Ingår i: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The use of analgesic antipyretics (ANAP) in children have long been a matter of controversy. Data on their practical use on an individual level has, however, been scarce. There are indications of possible effects on glucose homeostasis and immune function related to the use of ANAP. The aim of this study was to analyze patterns of analgesic antipyretic use across the clinical centers of The Environmental Determinants of Diabetes in the Young (TEDDY) prospective cohort study and test if ANAP use was a risk factor for islet autoimmunity. Methods: Data were collected for 8542 children in the first 2.5 years of life. Incidence was analyzed using logistic regression with country and first child status as independent variables. Holm's procedure was used to adjust for multiplicity of intercountry comparisons. Time to autoantibody seroconversion was analyzed using a Cox proportional hazards model with cumulative analgesic use as primary time dependent covariate of interest. For each categorization, a generalized estimating equation (GEE) approach was used. Results: Higher prevalence of ANAP use was found in the U.S. (95.7%) and Sweden (94.8%) compared to Finland (78.1%) and Germany (80.2%). First-born children were more commonly given acetaminophen (OR 1.26; 95% CI 1.07, 1.49; p = 0.007) but less commonly Non-Steroidal Anti-inflammatory Drugs (NSAID) (OR 0.86; 95% CI 0.78, 0.95; p = 0.002). Acetaminophen and NSAID use in the absence of fever and infection was more prevalent in the U.S. (40.4%; 26.3% of doses) compared to Sweden, Finland and Germany (p < 0.001). Acetaminophen or NSAID use before age 2.5 years did not predict development of islet autoimmunity by age 6 years (HR 1.02, 95% CI 0.99-1.09; p = 0.27). In a sub-analysis, acetaminophen use in children with fever weakly predicted development of islet autoimmunity by age 3 years (HR 1.05; 95% CI 1.01-1.09; p = 0.024). Conclusions: ANAP use in young children is not a risk factor for seroconversion by age 6 years. Use of ANAP is widespread in young children, and significantly higher in the U.S. compared to other study sites, where use is common also in absence of fever and infection.
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| 15. |
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| 16. |
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| 17. |
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| 18. |
- Storm, Tina, et al.
(författare)
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Renal phenotypic investigations of megalin-deficient patients : novel insights into tubular proteinuria and albumin filtration
- 2013
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Ingår i: Nephrology, Dialysis and Transplantation. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 28:3, s. 585-591
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe reabsorption of filtered plasma proteins, hormones and vitamins by the renal proximal tubules is vital for body homeostasis. Studies of megalin-deficient mice suggest that the large multi-ligand endocytic receptor megalin plays an essential role in this process. In humans, dysfunctional megalin causes the extremely rare Donnai-Barrow/Facio-Oculo-Acustico-Renal (DB/FOAR) syndrome characterized by a characteristic and multifaceted phenotype including low-molecular-weight proteinuria. In this study, we examined the role of megalin for tubular protein reabsorption in humans through analysis of proximal tubular function in megalin-deficient patients.MethodsDirect sequencing of the megalin-encoding gene (LRP2) was performed in a family in which three children presented with classical DB/FOAR manifestations. Renal consequences of megalin deficiency were investigated through immunohistochemical analyses of renal biopsy material and immunoblotting of urine samples.ResultsIn the patients, a characteristic urinary protein profile with increased urinary excretion of vitamin D-binding protein, retinol-binding protein and albumin was associated with absence of, or reduced, proximal tubular endocytic uptake as shown by renal immunohistochemistry. In the absence of tubular uptake, urinary albumin excretion was in the micro-albuminuric range suggesting that limited amounts of albumin are filtered in human glomeruli.ConclusionsThis study demonstrated that megalin plays an essential role for human proximal tubular protein reabsorption and suggests that only limited amounts of albumin is normally filtered in the human glomeruli. Finally, we propose that the characteristic urinary protein profile of DB/FOAR patients may be utilized as a diagnostic marker of megalin dysfunction.
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| 19. |
- Tegler, Gustaf, 1968-, et al.
(författare)
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4D-PET/CT with [11C]-PK11195 and [11C]-D-deprenyl does not identify the chronic inflammation in asymptomatic abdominal aortic aneurysms
- 2013
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Ingår i: European Journal of Vascular and Endovascular Surgery. - : Elsevier BV. - 1078-5884 .- 1532-2165. ; 45:4, s. 351-356
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesThe aim of this study was to investigate the relevance of inflammation in the pathogenesis of abdominal aortic aneurysm (AAA) in vivo with two novel positron emission tomography (PET) tracers: [11C]-PK11195 which targets the translocator protein (18 kDa) expressed on macrophages and [11C]-d-deprenyl with a yet unknown target receptor expressed in chronic inflammation.DesignProspective clinical study.Materials/methodsFive patients were examined with [11C]-PK11195-positron emission tomography/computed tomography (PET/CT) and 10 with [11C]-d-deprenyl-PET/CT. Nine large AAAs (54–66 mm) scheduled for repair and six small AAA (35–44 mm). All 15 patients were male and the AAAs were all asymptomatic. Regional activity was measured as standardised uptake values (SUVs) and retention index was calculated. Biopsies were taken from the aneurysm wall for histological examinations, in the nine patients operated on.ResultsNo aortic uptake was recorded on the visual inspection, neither with [11C]-PK11195 nor with [11C]-d-deprenyl. For [11C]-PK11195 the median SUV of the AAA wall was 0.9 (range 0.8–1.0) and for [11C]-d-deprenyl, 0.7 (range 0.4–1.2). No increased uptake was seen in the aneurysmal infrarenal aorta compared with the non-aneurysmal suprarenal aorta. Histological examination of the aneurysm wall showed high inflammatory cell infiltration with lymphocytes and macrophages.ConclusionsThe chronic inflammation observed in the vessel wall was not detectable with [11C]-PK11195 and [11C]-d-deprenyl. In order to study the relevance of the inflammation in the pathogenesis of AAA in vivo other PET tracers need to be investigated.
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| 20. |
- Tegler, Gustaf, et al.
(författare)
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Inflammation in the walls of asymptomatic abdominal aortic aneurysms is not associated with increased metabolic activity detectable by 18-fluorodeoxglucose positron-emission tomography
- 2012
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Ingår i: Journal of Vascular Surgery. - : Elsevier BV. - 0741-5214 .- 1097-6809. ; 56:3, s. 802-807
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:We hypothesized that the general inflammation observed in the wall of large, asymptomatic abdominal aortic aneurysms (AAAs) could be detected in vivo by 18-fluorodeoxglucose (FDG) positron-emission tomography (PET) and, if so, that this method could be used to study if active inflammation is an early pathogenetic finding in small AAAs detected by screening.METHODS:In this prospective clinical study, 12 men were examined with FDG-PET computed tomography. Seven had large asymptomatic AAAs (range, 52-66 mm) that required surgery, and five had small AAAs (range, 34-40 mm) under surveillance. In the surgery group, biopsy specimens were taken from the aneurysm wall for histologic examinations.RESULTS:Compared with normal segments of the aorta, liver, and blood and compared with healthy controls matched for age and sex, no increased FDG uptake, measured as standardized uptake value, was detected in any of the large or small AAAs. The SUVmean difference between infrarenal aorta and blood was -0.3 for cases and -0.1 for controls (P = .06). The corresponding differences between the infrarenal aorta and liver was -0.8 and -0.8 (P = .91) and between infrarenal aorta and suprarenal aorta was -0.2 and -0.1 for cases and controls, respectively (P = .20). The histologic examination of the aneurysm walls showed high inflammatory cell infiltration with T lymphocytes, B lymphocytes, and macrophages.CONCLUSIONS:The chronic inflammation observed in the wall of asymptomatic AAAs was not sufficiently metabolically active to result in an increased glucose metabolism detectable by FDG-PET by means of this standard protocol. To study the importance of inflammation in the pathogenesis of AAAs in vivo, PET tracers other than FDG need to be developed.
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| 21. |
- Wilbe, Maria, et al.
(författare)
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MuSK : a new target for lethal fetal akinesia deformation sequence (FADS).
- 2015
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Ingår i: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 52:3, s. 195-202
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Fetal akinesia deformation sequence syndrome (FADS, OMIM 208150) is characterised by decreased fetal movement (fetal akinesia) as well as intrauterine growth restriction, arthrogryposis, and developmental anomalies (eg, cystic hygroma, pulmonary hypoplasia, cleft palate, and cryptorchidism). Mutations in components of the acetylcholine receptor (AChR) pathway have previously been associated with FADS.METHODS AND RESULTS: We report on a family with recurrent fetal loss, where the parents had five affected fetuses/children with FADS and one healthy child. The fetuses displayed no fetal movements from the gestational age of 17 weeks, extended knee joints, flexed hips and elbows, and clenched hands. Whole exome sequencing of one affected fetus and the parents was performed. A novel homozygous frameshift mutation was identified in muscle, skeletal receptor tyrosine kinase (MuSK), c.40dupA, which segregated with FADS in the family. Haplotype analysis revealed a conserved haplotype block suggesting a founder mutation. MuSK (muscle-specific tyrosine kinase receptor), a component of the AChR pathway, is a main regulator of neuromuscular junction formation and maintenance. Missense mutations in MuSK have previously been reported to cause congenital myasthenic syndrome (CMS) associated with AChR deficiency.CONCLUSIONS: To our knowledge, this is the first report showing that a mutation in MuSK is associated with FADS. The results support previous findings that CMS and/or FADS are caused by complete or severe functional disruption of components located in the AChR pathway. We propose that whereas milder mutations of MuSK will cause a CMS phenotype, a complete loss is lethal and will cause FADS.
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